Phenylbutazone radical

A phenylbutazone radical has been identified spectrophotometrically using pulse radiolysis during which a solution of phenylbutazone was bombarded with hydroxyl radicals (Evans and Aruoma, unpublished work). It is therefore likely that ferryl systems oxidise the drug to free radical forms which cause oxidative damage to arachidonic acid and ai-antiproteinase. 

Peroxyl radicals are the species that propagate autoxidation of the unsaturated fatty acid residues of phospholipids (50). In addition, peroxyl radicals are intermediates in the metabolism of certain drugs such as phenylbutazone (51). Epoxidation of BP-7,8-dihydrodiol has been detected during lipid peroxidation induced in rat liver microsomes by ascorbate or NADPH and during the peroxidatic oxidation of phenylbutazone (52,53). These findings suggest that peroxyl radical-mediated epoxidation of BP-7,8-dihydrodiol is general and may serve as the prototype for similar epoxidations of other olefins in a variety of biochemical systems. In addition, peroxyl radical-dependent epoxidation of BP-7,8-dihydrodiol exhibits the same stereochemistry as the arachidonic acid-stimulated epoxidation by ram seminal vesicle microsomes. This not only provides additional... 

Phenylbutazone. - This anti-inflammatory drug inhibits prostaglandin H synthase. Earlier spin-trapping studies established that PB is oxidised to a carbon-centred radical by the peroxidase activity of the enzyme.175 The radical has since been trapped with MNP upon incubation of the drug with HRP. The intensity of the signal from the adduct was reduced by GSH, suggesting chemical repair of the radical by the thiol. The PB/HRP system induced lipid peroxidation in microsomes, which was suppressed by GSH.176... 

Bucher has described a test for anti-inflammatory compounds which involves the intraperitoneal injection of talc into guinea-pigs to produce peritonitis. One of the behavioural manifestations of this is inhibition of gnawing activity, which is restored to normal by various analgesic and antipyretic substances, especially pyrazolones. Phenylbutazone and amidopyrine are both active in doses as low as 5 mg/kg subcutaneously. Acetylsali-cylic acid is also active, but prednisolone affects the response only when given in high doses. This test was used to demonstrate anti-inflammatory activity in a series of pyrazolones in which the usual 3-methyl group is replaced by alkylsulphonamido radicals . The most active compound XXXI) is equal in efficacy to phenylbutazone. 

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